The cerebral cortex is particularly sensitive to experience-dependent plasticity during a well-defined critical period. To date, a number of studies have documented the functional and structural correlates of sensory deprivation during the critical period in visual cortex, but the mechanisms behind these changes are still not well understood. Previous DNA microarray analysis in the this lab identified components of the JAK/STAT immune signaling cascade, in particular STAT1, as being significantly upregulated in visual cortex during the critical period, after long term sensory deprivation. This signaling pathway has been well studied in the hematopoitic system as a mediator of the effects of the cytokine IFN-gamma in cell-mediated immunity. Although IFN-gamma signaling has also been implicated in a number of neurological disorders, including Down syndrome and Multiple Sclerosis, little is known of the function of this signaling pathway in the nervous system. In the proposed studies, physiological, anatomical, and imaging methods will be utilized to uncover the novel role of the JAK/STAT signaling pathway in cortical development and experience-driven plasticity. First, in vivo intrinsic signal optical imaging and single unit recording will be used to examine how modulation of this pathway affects activity-dependent changes in cortical connectivity and function. Anatomical and biochemical methods will be used to corroborate the microarray finding for elements of the JAK/STAT signaling cascade that are upregulated/downregulated during monocular deprivation, and identify in which cell type(s) these expression and signaling changes occur. Finally, in vivo two-photon imaging of visual cortex will be utilized to determine whether activated STAT1 modulates changes in spine dynamics during sensory deprivation. This proposal will address the possible role for an immune signaling pathway in the experience-dependent brain rewiring that occurs during development. My goal is to provide information on a potential mechanism of cortical development and plasticity, which may also be important for understanding neurological dysfunction in diseases of immune signaling. criticism that only slightly diminishes enthusiasm is the lack of a detailed plan for specific mentor-advisee evaluation/meetings (beyond a weekly general lab meeting) and advisory panel. [unreadable] [unreadable] [unreadable]